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I have been involved in the care and in studies of the Natural History and complications of Cardiac Transplantation since 1980.

In 1976, following a a year spent in the observation and care of children undergoing surgery for repair of congenital heart disease, I pursued a special interest in this area and participated in the care of adults with these lesions with our Pediatric Cardiologists and surgeons. I have maintained and extended my involvement with time and look forward to a growing proportion of these patients in my practice at Stanford.

Abstract

Rapamycin has been shown to reduce anatomical evidence of cardiac allograft vasculopathy, but its effect on coronary artery physiology is unknown.Twenty-seven patients without angiographic evidence of coronary artery disease underwent measurement of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) within 8 weeks and then 1 year after transplantation using a pressure sensor/thermistor-tipped guidewire. Measurements were compared between consecutive patients who were on rapamycin for at least 3 months during the first year after transplantation (rapamycin group, n = 9) and a comparable group on mycophenolate mofetil (MMF) instead (MMF group, n = 18).At baseline, there was no significant difference in FFR, CFR, or IMR between the 2 groups. At 1 year, FFR declined significantly in the MMF group (0.87 +/- 0.06 to 0.82 +/- 0.06, P = .009) but did not change in the rapamycin group (0.91 +/- 0.05 to 0.89 +/- 0.04, P = .33). Coronary flow reserve and IMR did not change significantly in the MMF group (3.1 +/- 1.7 to 3.2 +/- 1.0, P = .76; and 27.5 +/- 18.1 to 19.1 +/- 7.6, P = .10, respectively) but improved significantly in the rapamycin group (2.3 +/- 0.8 to 3.8 +/- 1.4, P < .03; and 27.0 +/- 11.5 to 17.6 +/- 7.5, P < .03, respectively). Multivariate regression analysis revealed that rapamycin therapy was an independent predictor of CFR and FFR at 1 year after transplantation.Early after cardiac transplantation, rapamycin therapy is associated with improved coronary artery physiology involving both the epicardial vessel and the microvasculature.

Abstract

Reninoma is a tumor of the renal juxtaglomerular cell apparatus that causes hypertension and hypokalemia via hypersecretion of renin. We describe a case of reninoma and provide a review of the literature, with a discussion emphasizing the diagnostic evaluation for such patients. The subject had persistent elevation of both plasma renin activity (PRA) and aldosterone. Imaging studies revealed the presence of a lesion in the renal cortex, which was further identified as a renin-producing lesion via selective venous catheterization following administration of an angiotensin-converting enzyme inhibitor (ACE-I). Following partial nephrectomy, the PRA and plasma aldosterone levels declined rapidly and the blood pressure and potassium supplementation requirements normalized. This case demonstrates the utility of both appropriate imaging studies and selective venous catheterization following provocative administration of an ACE-I for diagnosis.

Abstract

The ongoing shortage of donors for cardiac transplantation has led to a trend toward acceptance of donor hearts with some structural abnormalities including left ventricular hypertrophy. To evaluate the outcome in recipients of donor hearts with increased left ventricular wall thickness (LVWT), we retrospectively analyzed data for 157 cardiac donors and respective recipients from January 2001 to December 2004. There were 47 recipients of donor heart with increased LVWT >or=1.2 cm, which constituted the study group and 110 recipients of a donor heart with normal LVWT < 1.2 cm that formed the control group. At 3 +/- 1.5 years, recipient survival was lower (50% vs. 82%, p = 0.0053) and incidence of allograft vasculopathy was higher (50% vs. 22%, p = 0.05) in recipients of donor heart with LVWT > 1.4 cm as compared to LVWT 1.4 cm (p = 0.003), recipient preoperative ventricular assist device (VAD) support (p = 0.04) and bypass time > 150 min (p = 0.05) were predictors of reduced survival. Our results suggest careful consideration of donor hearts with echocardiographic evidence of increased LVWT in the absence of hypovolemia, because they may be associated with poorer outcomes; such hearts should potentially be reserved only for the most desperately ill recipients.

Abstract

Pulmonary infection with Nocardia is an uncommon but serious infection found in immunocompromised patients. We describe a rapidly progressive pulmonary nocardiosis in a heart transplant patient. We then review the common clinical features of Nocardia infection in transplant recipients, outlining the challenges in its diagnosis and management. We also review the differences between Pneumocystis jiroveci prophylaxis regimens with respect to concomitant prophylaxis of Nocardia and other opportunistic infections.

Abstract

Orthotopic heart transplantation is considered an effective treatment for patients with refractory heart failure. The long-term survival of orthotopic heart transplantation recipients has increased over the last several decades, but many long-term survivors of orthotopic heart transplantation develop graft atherosclerosis and associated left ventricular dysfunction. The risk of sudden cardiac death in long-term survivors of orthotopic heart transplantation with these complications is believed to be high. There are no data on the usefulness of implantable cardioverter-defibrillators (ICDs) in this population; therefore, we report our early experience with ICD placement in such patients.The purpose of this study was to examine the use of ICDs in adults who are long-term survivors of heart transplantation.We retrospectively reviewed all adult patients who underwent orthotopic heart transplantation at Stanford University Hospital (Stanford, CA, USA) from 1980 to 2004. All patients who received an ICD after transplant were included in this study. We reviewed demographic data, medical history, ejection fraction, presence of graft atherosclerosis, indication for ICD placement, and any device therapy delivered.Of the 925 patients who had orthotopic heart transplantation during this time period, 493 patients were alive at the beginning of the year 2000. Of these patients, 10 ( approximately 2%) had subsequent placement of an ICD. All 10 patients were male. The average age at orthotopic heart transplantation was 37.8 years. The average age at ICD placement was 50.5 years. The average time from orthotopic heart transplantation to ICD placement was 14.6 years. The average ejection fraction at the time of implant was 46.5%. Five of the 10 patients had a low ejection fraction (within this subgroup, the average ejection fraction was 31%, range 15%-45%) and graft atherosclerosis. ICDs were placed because of symptomatic episodes of ventricular tachycardia (3 patients), low ejection fraction and severe graft atherosclerosis without symptoms (3 patients), and after thorough evaluation for otherwise unexplained syncope (4 patients). The average follow-up after device implantation was 13 months. Complications related to ICD placement were an infected ICD system requiring explant in one patient and a lead fracture in another patient. Three patients had subsequent appropriate shocks for ventricular arrhythmias, and one patient underwent a second orthotopic heart transplantation. One patient died of malignancy.Use of the ICD in long-term survivors of orthotopic heart transplantation should be considered in appropriately selected patients. Further data are needed regarding ICD use in this population.

Abstract

Post-transplantation lymphoproliferative disease (PTLD) is an important source of morbidity and mortality in transplant recipients, with a reported incidence of 0.8% to 20%. Risk factors are thought to include immunosuppressive agents and viral infection. This study attempts to evaluate the impact of different immunosuppressive regimens, ganciclovir prophylaxis and other potential risk factors in the development of PTLD.We reviewed the records of 1026 (874 heart, 152 heart-lung) patients who underwent transplantation at Stanford between 1968 and 1997. Of these, 57 heart and 8 heart-lung recipients developed PTLD. During this interval, 4 different immunosuppressive regimens were utilized sequentially. In January 1987, ganciclovir prophylaxis for cytomegalovirus serologic-positive patients was introduced. Other potential risk factors evaluated included age, gender, prior cardiac diagnoses, HLA match, rejection frequency and calcium-channel blockade.No correlation of development of PTLD was found with different immunosuppression regimens consisting of azathioprine, prednisone, cyclosporine, OKT3 induction, tacrolimus and mycophenolate mofetil. A trend suggesting an influence of ganciclovir on the prevention of PTLD was not statistically significant (p = 0.12). Recipient age and rejection frequency, as well as high-dose cyclosporine immunosuppression, were significantly (p < 0.02) associated with PTLD development. The prevalence of PTLD at 13.3 years was 15%.The overall incidence of PTLD was 6.3%. It was not altered by sequential modifications in treatment regimens. Younger recipient age and higher rejection frequency were associated with increased PTLD occurrence. The 15% prevalence of PTLD in 58 long-term survivors was unexpectedly high.

Abstract

The discovery of cyclosporine A (CsA) was a major development in the evolution of organ transplantation. In renal transplantation use of CsA improved graft survival such that HLA-matching is no longer as important and determinant as before. Liver transplantation prior to the arrival of CsA was almost abandoned by Starzl because of uncontrollable rejection. Hearth transplantation, after initial enthusiasm, was soon restricted to few centers as the difficulties in caring for these patients became apparent. Availability of CsA allowed more than 2500 hearth transplants to be performed annually today. At Stanford initially cardiac transplant survival at one year was 40% and at 5 years was approx 20%. The best results in patients treated with azathioprine-prednisone, just prior to the introduction of cyclosporine, were 65% and 40%. At present survival is 83% at 1 year and 50% at 6-7 years, as in other active centers around the world. CsA is the first drug specifically developed to target immunocompetent T-lymphocytes, and is the gold standard model for other new drugs. Its action is modification of rejection, so that when it occurs it is less acute in onset and less fulminant. The prevalence and mortality of infections have also been reduced. The major drawback of cyclosporine is nephrotoxicity: all patients undergo a progressive decline in creatinine clearance and within one year 90% have hypertension. A second problem is post-transplant lymphoproliferative disease, that takes the form of an aggressive and potentially lethal B-cell lymphoma appearing most commonly within one year from surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Cardiac transplantation has now become accepted therapy for the treatment of end-stage heart disease in both children and adults, and literally thousands of patients are bearers of cardiac grafts. Because of these patients' susceptibility to infections, rejection, coronary disease, and malignancy, as well as to serious illnesses unrelated to their transplantation, they will often be encountered at hospital centers both close to their homes and distant from the site of their surgery. The intensive care unit physician's role will be a demanding one when caring for these patients because of the broad differential diagnosis of infections, frequency of drug interactions and altered immunosuppression, and continuous uncertainty regarding the possibility of rejection, particularly during the first year after transplantation.

Abstract

Physiologic and morphologic techniques were used to study kidneys of cardiac transplant recipients treated with either low-dose (low-CsA) or high-dose (high-CsA) cyclosporine. After 12 months both low-CsA (4.6 +/- 0.4) and high-CsA (6.3 +/- 0.3 mg/Kg/24 hr, p less than 0.01) were associated with azotemia and hypertension; GFR with each regimen was depressed below values in a third group treated without CsA (no-CsA) by 40-47%, while corresponding renal vascular resistance was elevated greater than 2-fold (P less than 0.01). Morphologic changes in both CsA groups included an obliterative arteriolopathy with downstream collapse or sclerosis of glomeruli. Determination of renal arcuate vein occlusion pressure revealed an increasing renal artery-to-peritubular capillary pressure gradient between 1 and 12 months of CsA therapy. Fractional clearances of dextrans of graded size were elevated at each time compared with the no-CsA group. Analysis of dextran transport with an isoporous membrane model indicates that transglomerular hydraulic pressure difference (delta P) approximated 39 with no-CsA, but was reduced with low-CsA therapy to about 30 at 1 month, and about 34 mmHg after 12 months. We conclude that chronic CsA therapy induces constriction and eventual occlusion of afferent arterioles, causing downstream glomerular damage that is irreversible. Low versus high dosage of CsA confers only marginal protection against this serious microvascular injury.